Investigation of mechanisms on autoinflammatory diseases caused by NLRP1 mutation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20912
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Juntendo University
• Principal Investigator: Taiki Ando 順天堂大学, 医学部, 助手 (10912644)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: インフラマソーム / 肝臓線維化

Outline of Final Research Achievements

We attempted to elucidate the mechanisms by which the NLRP1 point mutation, identified in a rare disease patient, caused liver cirrhosis. We demonstrated that NLRP1 inflammasome is constitutively activated in liver cell lines derived from this patient; however, we were not able to clarify the causal relationship between the NLRP1 inflammasome activation in hepatocytes and liver cirrhosis. We then generated the mice expressing this NLRP1 mutation specifically in hepatocytes. However, these mice neither exhibited NLRP1 inflammasome activation in hepatocytes nor liver abnormalities such as liver fibrosis. Accordingly, it was possible to speculate that in this patient, any infection and/or drug administration had triggered NLRP1 inflammasome activation, induced by this mutation, in hepatocytes. Further examination will be required to understand the relevant mechanisms.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

我々が同定した新規のNLRP1変異に関する本研究成果はNLRP1変異による自己炎症性疾患という概念の確立に寄与した。このように、本研究成果は学術的意義が高いと考えられる。また、インフラマソームを活性化させる機序の解明は特定の自己炎症性疾患の治療薬開発につながる可能性があり、本研究成果の社会的意義も高いと考えられる。